Department of Pathology, New York University Grossman School of Medicine, NYU Langone Health, New York, New York.
The Laura and Isaac Perlmutter Cancer Center, New York University Langone Health, New York, New York.
Clin Cancer Res. 2022 Aug 2;28(15):3182-3184. doi: 10.1158/1078-0432.CCR-22-0541.
4-1BB has been considered a promising target in cancer immunotherapy for decades. Nevertheless, early 4-1BB-targeted agents demonstrated significant liver immuno-toxicity. A new wave of 4-1BB-based therapy is being developed to circumvent hepatotoxicity with a bispecific molecule that directs 4-1BB agonism to the tumor microenvironment by targeting tumor-associated immune checkpoint molecule PD-L1. See related article by Peper-Gabriel et al., p. 3387.
数十年来，4-1BB 一直被认为是癌症免疫疗法中有前途的靶点。然而，早期的 4-1BB 靶向药物表现出显著的肝脏免疫毒性。目前正在开发新一代的 4-1BB 为基础的疗法，通过靶向肿瘤相关免疫检查点分子 PD-L1，用双特异性分子将 4-1BB 激动作用导向肿瘤微环境，从而避免肝毒性。见 Peper-Gabriel 等人的相关文章，第 3387 页。
